Role of transient receptor potential vanilloid 4 channels in an ovalbumin-induced murine food allergic model.

The prevalence of food allergy (FA) has increased worldwide but an effective therapeutic strategy has not been established. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive nonselective cation channel, is mainly expressed in the epithelium of various organs. The present study investigated the role of TRPV4 in the pathogenesis of an ovalbumin (OVA)-induced FA model in mice. Wild-type (WT) and TRPV4-deficient (TRPV4KO) mice were sensitized and challenged by OVA to establish FA model. Intestinal tissue samples were processed for biochemical, molecular, and image analyses. Intestinal permeability and antigen uptake assay were conducted using FITC-dextran and OVA-FITC, respectively. TRPV4 was expressed in the colonic epithelium in normal and OVA-treated WT mice. Repeated oral administration of OVA to mice induced systemic allergic symptoms, diarrhea, upregulation of T helper 2 cytokines, OVA-specific immunoglobulin, and FA-related inflammatory cells. These responses were significantly augmented in TRPV4KO mice compared with WT mice. After the induction of FA, the intestinal permeability was significantly increased in TRPV4KO mice compared with WT mice. The expressions of the tight junction protein occludin and adherence junction protein E-cadherin in the colon were significantly lower in TRPV4KO mice compared with WT mice under normal and FA conditions. In addition, the uptake of OVA by CD11c-positive cells was significantly increased in TRPV4KO mice compared with WT mice under FA conditions. These results suggest that epithelial TRPV4 protects against OVA-induced FA symptoms by suppressing the penetration of allergens by maintaining epithelial barrier functions.

Suppression of Mast Cell Activation by GPR35: GPR35 Is a Primary Target of Disodium Cromoglycate.

Mast cell stabilizers, including disodium cromoglycate (DSCG), were found to have potential as the agonists of an orphan G protein-coupled receptor, GPR35, although it remains to be determined whether GPR35 is expressed in mast cells and involved in suppression of mast cell degranulation. Our purpose in this study is to verify the expression of GPR35 in mast cells and to clarify how GPR35 modulates the degranulation. We explored the roles of GPR35 using an expression system, a mast cell line constitutively expressing rat GPR35, peritoneal mast cells, and bone marrow-derived cultured mast cells. Immediate allergic responses were assessed using the IgE-mediated passive cutaneous anaphylaxis (PCA) model. Various known GPR35 agonists, including DSCG and newly designed compounds, suppressed IgE-mediated degranulation. GPR35 was expressed in mature mast cells but not in immature bone marrow-derived cultured mast cells and the rat mast cell line. Degranulation induced by antigens was significantly downmodulated in the mast cell line stably expressing GPR35. A GPR35 agonist, zaprinast, induced a transient activation of RhoA and a transient decrease in the amount of filamentous actin. GPR35 agonists suppressed the PCA responses in the wild-type mice but not in the GPR35-/- mice. These findings suggest that GPR35 should prevent mast cells from undergoing degranulation induced by IgE-mediated antigen stimulation and be the primary target of mast cell stabilizers. SIGNIFICANCE STATEMENT: The agonists of an orphan G protein-coupled receptor, GPR35, including disodium cromoglycate, were found to suppress degranulation of rat and mouse mature mast cells, and their antiallergic effects were abrogated in the GPR35-/- mice, indicating that the primary target of mast cell stabilizers should be GPR35.

Pattern recognition receptors involved in the immune system of hagfish (Eptatretus burgeri).

The initial defense against invading pathogenic microbes is the activation of innate immunity by binding of pattern recognition receptors (PRRs) to pathogen associated molecular patterns (PAMPs). To explain the action of PRRs from hagfish, one of the extant jawless vertebrates, we purified the GlcNAc recognition complex (GRC) from serum using GlcNAc-agarose. The GRC comprises four proteins of varying molecular masses: 19 kDa, 26 kDa, 27 kDa, and 31 kDa. Exposure of Escherichia coli to the GRC led to the phagocytic activation of macrophages, revealing the opsonic function of the GRC. The GRC in serum formed a large complex with a molecular mass of approximately 1200 kDa. The GRC bound to Escherichia coli but not to rabbit red blood cells, despite both having GlcNAc on their surface. These structural and binding properties are similar to those of mannose-binding lectin (MBL). The amino acid sequence of a portion of the 31 kDa protein in the GRC matched the amino acid sequence of variable lymphocyte receptor (VLR)-B in some place. According to the Western blot analysis, the 31 kDa protein was recognized by the anti-hagfish VLR-B antiserum. Based on the results, it appears that the GRC functions as a PRR like MBL and that its 31 kDa protein has a structure similar to that of VLR-B.

Transient receptor potential melastatin 2 is involved in trinitrobenzene sulfonic acid-induced acute and chronic colitis-associated fibrosis progression in mice.

Crohn's disease, a chronic and recurrent gastrointestinal disease, frequently causes intestinal fibrosis. Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is activated by reactive oxygen species. This study investigated the role of TRPM2 in acute colitis and chronic colitis-associated fibrosis progression. Acute colitis and chronic colitis-associated fibrosis were induced in TRPM2-deficient (TRPM2KO) and wild-type (WT) mice through single and repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Bone marrow-derived macrophages (BMDMs) from WT and TRPM2KO mice were stimulated using H2O2. In WT mice, a single TNBS injection induced acute colitis with upregulated inflammatory cytokines/chemokines and Th1/Th17-related cytokines, while repeated TNBS injections induced chronic colitis-associated fibrosis with upregulation of fibrogenic factors and Th2-related cytokines. Acute colitis and chronic colitis-associated fibrosis with cytokines/chemokine upregulation and fibrogenic factors were considerably suppressed in TRPM2KO mice. Treating BMDMs with H2O2 increased cytokine/chemokine expression and JNK, ERK, and p38 phosphorylation; however, these responses were significantly less in TRPM2KO than in WT mice. These findings suggest that TRPM2 contributes to acute colitis progression via Th1/Th17-mediated immune responses. Furthermore, TRPM2 may be directly involved in colitis-associated fibrosis induction, likely due to the regulation of Th2/TGF-ß1-mediated fibrogenesis in addition to a consequence of acute colitis progression.

Neutrophil extracellular trap induction through peptidylarginine deiminase 4 activity is involved in 2,4,6-trinitrobenzenesulfonic acid-induced colitis.

Neutrophil extracellular traps (NETs) are induced in the innate immune response against infectious agents and are also implicated in the pathogenesis of various cancers and autoimmune diseases. Peptidylarginine deiminase 4 (PAD4), an enzyme that converts arginine to citrulline, is also involved in NET formation. In this study, we investigated the pathogenic effect of PAD4 on NETs in inflammatory bowel disease using a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. PAD4-deficient (PAD4KO) mice were generated by CRISPR-Cas9-mediated genomic editing. NETs were triggered in peritoneal neutrophils obtained from wild-type mice by A23187 (a calcium ionophore), but these responses were completely abolished in the PAD4KO mice. Experimental colitis was induced in wild-type and PAD4KO mice via an intrarectal injection of TNBS. TNBS injection resulted in body weight loss, extensive colonic erosion, and ulceration in wildtype mice. However, these responses were significantly attenuated following the administration of Cl-amidine (an inhibitor of pan-PADs) and DNase I (an inhibitor of NET formation), in combination with PAD4KO in mice. TNBS-induced increases in myeloperoxidase activity, inflammatory cytokine expression, and NET formation in the colon were significantly reduced following the administration of Cl-amidine, DNase I injection, and PAD4KO. These findings suggest that NET formation contributes to the pathogenesis of TNBS-induced colitis via PAD4. Thus, PAD4 is a promising target for the treatment of inflammatory bowel disease.

Transient Receptor Potential Ankyrin 1 in Taste Nerve Contributes to the Sense of Sweet Taste in Mice.

Transient receptor potential (TRP) channels play a significant role in taste perception. TRP ankyrin 1 (TRPA1) is present in the afferent sensory neurons and is activated by food-derived ingredients, such as Japanese horseradish, cinnamon, and garlic. The present study aimed to investigate the expression of TRPA1 in taste buds, and determine its functional roles in taste perception using TRPA1-deficient mice. In circumvallate papillae, TRPA1 immunoreactivity colocalised with P2X2 receptor-positive taste nerves but not with type II or III taste cell markers. Behavioural studies showed that TRPA1 deficiency significantly reduced sensitivity to sweet and umami tastes, but not to salty, bitter, and sour tastes, compared to that in wild-type animals. Furthermore, administration of the TRPA1 antagonist HC030031 significantly decreased taste preference to sucrose solution compared to that in the vehicle-treated group in the two-bottle preference tests. TRPA1 deficiency did not affect the structure of circumvallate papillae or the expression of type II or III taste cell and taste nerve markers. Adenosine 5'-O-(3-thio)triphosphate evoked inward currents did not differ between P2X2- and P2X2/TRPA1-expressing human embryonic kidney 293T cells. TRPA1-deficient mice had significantly decreased c-fos expression in the nucleus of the solitary tract in the brain stem following sucrose stimulation than wild-type mice. Taken together, the current study suggested that TRPA1 in the taste nerve contributes to the sense of sweet taste in mice.

Deficiency of leukotriene B4 receptor type 1 ameliorates ovalbumin-induced allergic enteritis in mice.

Leukotriene B4 receptor type 1 (BLT1), a high-affinity receptor for leukotriene B4 (LTB4), plays an important role in inflammatory responses, including allergic airway inflammation. In this study, we examined the effect of genetic BLT1 deletion (BLT1KO) on ovalbumin (OVA)-induced allergic enteritis in mice to determine the pathogenic role of LTB4/BLT1 in allergic enteritis, a gastrointestinal form of food allergy. Repeated oral OVA challenges after sensitization with OVA and aluminium potassium sulphate induced allergic enteritis, characterized by systemic allergic symptoms (scratching, immobility and swelling), diarrhoea, colonic oedema and colonic goblet cell hyperplasia, accompanied by increased colonic peroxidase activity, colonic inflammatory cytokine expression and increased serum OVA-specific IgE levels. The severity of enteritis was significantly attenuated in BLT1KO mice compared with wild-type (WT) mice, without an increase in serum OVA-specific IgE levels. The accumulation of neutrophils, eosinophils, M2-macrophages, dendritic cells, CD4+ T cells and mast cells was observed in the colonic mucosa of allergic enteritis, and such accumulation was significantly lower in BLT1KO mice than in WT mice. BLT1 expression was upregulated and colocalized mostly in neutrophils and partly in eosinophils and dendritic cells in the colonic mucosa of allergic enteritis. These findings indicate that BLT1 deficiency ameliorates OVA-induced allergic enteritis in mice and that LTB4/BLT1 contributes to neutrophil and eosinophil accumulation in the allergic colonic mucosa. Therefore, BLT1 is a promising drug target for treating food allergies.

Immunohistochemical characterization of transient receptor potential vanilloid types 2 and 1 in a trinitrobenzene sulfonic acid-induced rat colitis model with visceral hypersensitivity.

Transient receptor potential vanilloid type 2 (TRPV2) and type 1 (TRPV1) are originally identified as heat-sensitive TRP channels. We compared the expression patterns of TRPV2 and TRPV1 in the rat distal colon and extrinsic primary afferent neurons, and investigated their roles in visceral hypersensitivity in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rats. Both TRPV2 and TRPV1 expressions in the colon, dorsal root ganglion (DRG), and nodose ganglion (NG) were significantly upregulated in the TNBS-induced colitis model. TRPV2 cell bodies co-localized with the intrinsic primary afferent marker NeuN and the inhibitory motor neuronal marker nNOS in the myenteric plexus. TRPV2 expressions were further detected in the resident macrophage marker ED2 in the mucosa. In contrast, no TRPV1-expressing cell bodies were detected in the myenteric plexus. Both TRPV2- and TRPV1-positive cell bodies in the DRG and NG were double-labeled with the neuronal retrograde tracer fluorescent fluorogold. Large- and medium-sized TRPV2-positive neurons were labeled with the A-fiber marker NF200, calcitonin gene-related peptide (CGRP), and substance P (SP) in the DRG while small-sized TRPV1-positive neurons were labeled with the C-fiber markers IB4, CGRP, and SP. TRPV2- and TRPV1-positive NG neurons were labeled with NF200 and IB4. TNBS treatment increased p-ERK1/2-positive cells in TRPV2 and TRPV1 neurons but did not affect the TRPV2 and TRPV1 subpopulations in the DRG and NG. Both TRPV2 and TRPV1 antagonists significantly alleviated visceral hypersensitivity in TNBS-induced colitis model rats. These findings suggest that intrinsic/extrinsic TRPV2- and extrinsic TRPV1-neurons contribute to visceral hypersensitivity in an experimental colitis model.

Repeated psychological stress, chronic vicarious social defeat stress, evokes irritable bowel syndrome-like symptoms in mice.

Increasing evidence has demonstrated that emotional states and intestinal conditions are inter-connected in so-called "brain-gut interactions." Indeed, many psychiatric disorders are accompanied by gastrointestinal symptoms, such as the irritable bowel syndrome (IBS). However, the functional connection remains elusive, partly because there are few useful experimental animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as the chronic vicarious social defeat stress (cVSDS) model mice, which we prepared using exposure to repeated psychological stress, thereafter examining their intestinal conditions. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over one month after the stress session. On the other hand, the pathological evaluations of the histological and inflammatory scores of naive and cVSDS model mice did not differ. Furthermore, keishikashakuyakuto-a kampo medicine clinically used for the treatment of IBS-normalized the intestinal motility change in cVSDS model mice. Our results indicate that cVSDS model mice present IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organic lesion. We therefore propose the cVSDS paradigm as a novel animal model of IBS with wide validity, elucidating the correlation between depressive states and intestinal abnormalities.

[Effects of Changing the Source-to-image Receptor Distance Parameter of Scattered X-ray Correction after Exposure on Image Quality in Portable Chest Radiography].

PURPOSE: To validate the effects of changing the source-to-image receptor distance (SID) parameter of scattered X-ray correction after exposure on the image quality in portable chest radiography. METHODS: The actual SID and tube current-time product (mAs) were varied such that the direct X-ray dose to a flat panel detector (FPD) remained constant. We created two groups as follows: Group A (with the SID parameter unchanged) and Group B (with the SID parameter changed to the actual SID after a phantom chest exposure). The image contrast ratio and standard deviation (SD) were measured on the chest radiographs for physical assessment. Observer studies were performed by seven radiological technologists. Scheffé's (Ura) paired comparison methods were performed with image contrast, noise, and overall assessment as the assessment items. Receiver operating characteristic (ROC) analysis for lung nodules was performed. RESULTS: The image contrast ratio and SD in Group A changed, whereas the changes in Group B were less than those in Group A for both these properties. The observer study with Scheffé's methods showed a statistically significant difference (p<0.05) for all assessment items in Group A but not in Group B. The ROC analysis did not indicate any statistically significant differences in either group. CONCLUSION: Changing the SID parameter of scattered X-ray correction after exposure can possibly maintain image contrast and noise in portable chest radiography if the actual SID changes.

Factors Affecting Incomplete L5/S Posterior Lumbar Interbody Fusion, Including Spinopelvic Sagittal Parameters.

STUDY DESIGN: Retrospective observational study. PURPOSE: In this study we identify risk factors, including patient demographics, sagittal parameters, and clinical examinations, affecting incomplete L5/S posterior lumbar interbody fusion (PLIF). OVERVIEW OF LITERATURE: The lumbosacral spine is considered to have an interbody fusion rate lower than that of the lumbar spine, but few studies have investigated the cause, including investigating the pelvis. We believe that pelvic morphology can affect L5/S interbody fusion of the lumbosacral spine. METHODS: We observed 141 patients (61 men, 80 women; average age, 65.8 years) who had undergone PLIF and checked for the presence of L5/S interbody fusion. We investigated factors such as age, gender, the presence of diffuse idiopathic skeletal hyperostosis (DISH), fusion level, and grade 2 osteotomy, as well as pre-, post-, and post-preoperative L5/S disk height and angle, lumbar lordosis, Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and pelvic incidence (PI), comparing those with and without L5/S interbody fusion. In addition, we analyzed the patients classified into short-level (n=111) and multi-level fusion groups (n=30). RESULTS: Overall, the L5/S interbody fusion rate was 70% (short-level, 78%; multi-level, 40%). Age and pre- and post-preoperative L5/S disk angle were significantly different in each fusion level group. DISH presence, grade 2 osteotomy, and postoperative VAS and JOA scores were significantly different in the short-level fusion group, whereas PI was significantly different in the multi-level fusion group. CONCLUSIONS: Incomplete union after L5/S PLIF correlates with advanced age, many fusion levels, and a large value of preoperative and a small value of post-preoperative L5/S disk angles.

Juvenile social defeat stress exposure favors in later onset of irritable bowel syndrome-like symptoms in male mice.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. Traumatic stress during adolescence increases the risk of IBS in adults. The aim of this study was to characterize the juvenile social defeat stress (SDS)-associated IBS model in mice. Juvenile mice were exposed to an aggressor mouse for 10 min once daily for 10 consecutive days. Behavioral tests, visceral sensitivity, immune responses, and fecal bacteria in the colon were evaluated in 5 weeks after SDS exposure. Social avoidance, anxiety- and depression-like behavior, and visceral hypersensitivity were observed. Juvenile SDS exposure significantly increased the number of 5-HT-containing cells and calcitonin gene-related peptide-positive neurons in the colon. The gut microbiota was largely similar between the control and juvenile SDS groups. The alterations in fecal pellet output, bead expulsion time, plasma corticosterone concentration, and colonic 5-HT content in response to restraint stress were exacerbated in the juvenile SDS group compared with the control group. The combination of juvenile SDS and restraint stress increased the noradrenaline metabolite 3-Methoxy-4-hydroxyphenylglycol (MHPG) content and MHPG/noradrenaline ratio in the amygdala when compared with restraint stress in control mice. These results suggest that juvenile SDS exposure results in later onset of IBS-like symptoms.

Protective Effect of TRPM8 against Indomethacin-Induced Small Intestinal Injury via the Release of Calcitonin Gene-Related Peptide in Mice.

Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by mild cooling and chemical agents including menthol. Nonsteroidal anti-inflammatory drugs have antipyretic, analgesic effects, and they can cause stomach and small intestinal injury. The current study investigated the role of TRPM8 in the pathogenesis of indomethacin-induced small intestinal injury. In male TRPM8-deficient (TRPM8KO) and wild-type (WT) mice, intestinal injury was induced via the subcutaneous administration of indomethacin. In addition, the effect of WS-12, a specific TRPM8 agonist, was examined in TRPM8KO and WT mice with indomethacin-induced intestinal injury. TRPM8KO mice had a significantly higher intestinal ulcerogenic response to indomethacin than WT mice. The repeated administration of WS-12 significantly attenuated the severity of intestinal injury in WT mice. However, this response was abrogated in TRPM8KO mice. Furthermore, in TRPM8-enhanced green fluorescent protein (EGFP) transgenic mice, which express EGFP under the direction of TRPM8 promoter, the EGFP signals in the indomethacin-treated intestinal mucosa were upregulated. Further, the EGFP signals were commonly found in calcitonin gene-related peptide (CGRP)-positive sensory afferent neurons and partly colocalized with substance P (SP)-positive neurons in the small intestine. The intestinal CGRP-positive neurons were significantly upregulated after the administration of indomethacin in WT mice. Nevertheless, this response was abrogated in TRPM8KO mice. In contrast, indomethacin increased the expression of intestinal SP-positive neurons in not only WT mice but also TRPM8KO mice. Thus, TRPM8 has a protective effect against indomethacin-induced small intestinal injury. This response may be mediated by the upregulation of CGRP, rather than SP.

A quinazoline-based bromodomain inhibitor, CN210, ameliorates indomethacin-induced ileitis in mice by inhibiting inflammatory cytokine expression.

Inhibitors of bromodomain and extra-terminal motif (BET) proteins are emerging epigenetic therapeutics that suppress gene expressions that drive cancer and inflammation. The present study examined anti-inflammatory effects of a quinazoline-based BET inhibitor, CN210, in a murine ileitis model. CN210 was given orally 30 min before and 24 h after a subcutaneous administration of indomethacin. Macroscopic and histological evidences of ileitis, mucosal myeloperoxidase (MPO) activity and cytokine expressions were evaluated 48 h after the indomethacin administration. To further characterize the anti-inflammatory pathways modulated by CN210, its effects on RAW264 cells treated with lipopolysaccharide (LPS) were investigated. Competitive ligand binding and docking studies of CN210 to CREB-binding protein (CBP) and p300 were also performed. Oral administration of CN210 significantly reduced the severity of ileitis, normalized both proinflammatory MPO activity and concomitant cytokine expressions induced by indomethacin administration. Furthermore, CN210 attenuated the expression of cytokines and reversed the activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPK) induced by LPS. Competitive ligand binding assays showed that CN210 bound to the bromodomains of two paralogous histone acetyltransferases, CBP and p300, in addition to the bromodomains of BET proteins. Docking studies of CN210 to the bromodomains of CBP and p300 showed a similarity to the binding mode of SGC-CBP30, a specific CBP/p300 inhibitor. CN210 ameliorates indomethacin-induced ileitis by inhibiting the expression of inflammatory cytokines through the attenuation of NF-κB and MAPK pathways. CN210 thus represents a new mode of therapy for non-steroidal anti-inflammatory drug-induced ileitis and inflammatory bowel disease.

Role of transient receptor potential vanilloid subtype 2 in lower oesophageal sphincter in rat acid reflux oesophagitis.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. In the present study, we investigated TRP vanilloid subfamily member 2 (TRPV2) expression in lower oesophageal sphincter (LES) and its involvement in acid reflux oesophagitis in rats. Expression of TRPV2 and nerve growth factor mRNAs was significantly enhanced in LES of rats with reflux oesophagitis compared with normal rats. TRPV2 was mainly expressed in inhibitory motor neurons, and partly in intrinsic and extrinsic primary afferent neurons, and macrophages in LES of normal and reflux oesophagitis rats. Number of TRPV2-immunopositive nerve fibres was significantly increased, but that of nNOS-, CGRP-, and PGP9.5-nerve fibres was not changed in reflux oesophagitis compared with normal group. Probenecid produced nitric oxide production and relaxation in LES and this response was significantly enhanced in oesophagitis compared with normal group. Probenecid-induced relaxant effect was blocked by a TRPV2 inhibitor, tranilast, and a NOS inhibitor, NG-nitro-l-arginine methyl ester, in reflux oesophagitis rats. Oral administration of tranilast significantly improved body weight loss, oesophageal lesions, and epithelial thickness in oesophagitis model. These results suggest that up-regulation of TRPV2 in inhibitory motor neurons is involved in LES relaxation in oesophagitis model. TRPV2 inhibition might be beneficial for treatment of GERD.

Early functional recovery after two-stage surgery with an allogenic bone graft for baseplate loosening in reverse shoulder arthroplasty: a case report.

OBJECTIVES: Reverse shoulder arthroplasty (RSA) for cuff tear arthropathy results in good shoulder function. However, RSA is associated with several complications, including infection, dislocation of the shoulder joint, implant loosening, and axillary nerve palsy. Several problems may also occur on the glenoid side, including bone defects of the glenoid, baseplate loosening, and displacement of the sphere. Herein, we report a 79-year-old man who obtained early functional recovery following a two-stage operation with an allogenic bone graft to treat baseplate loosening and a glenoid bone defect after RSA. CASE REPORT: The patient presented with pain during motion and limited active shoulder joint movement 5 weeks after undergoing RSA for cuff tear arthropathy. CT revealed baseplate loosening and a glenoid bone defect; these complications were treated via a two-stage operation. The first stage comprised the removal of all implants and the grafting of allogenic bone from the femoral head into the glenoid defect. Six months later, CT confirmed complete union of the grafted bone and glenoid. The second stage comprised the re-insertion of all implants. Two months after the last operation, the active shoulder range of motion of the affected side was almost identical to that of the contralateral side. CONCLUSION: Good early functional recovery was obtained using a two-stage operation for baseplate loosening after RSA. Allogenic bone grafting was effective in the reconstruction of the glenoid defect.

Risk Factors Affecting Cage Retropulsion into the Spinal Canal Following Posterior Lumbar Interbody Fusion: Association with Diffuse Idiopathic Skeletal Hyperostosis.

STUDY DESIGN: This was a retrospective observational study. PURPOSE: We identify risk factors, including physical and surgical factors, and comorbidities affecting cage retropulsion following posterior lumbar interbody fusion (PLIF). OVERVIEW OF LITERATURE: Diffuse idiopathic skeletal hyperostosis (DISH) is considered a risk factor for reoperation after PLIF. We evaluated the effect of DISH on cage retropulsion into the spinal canal, which may require surgical revision for severe neurological disorders. METHODS: A total of 400 patients (175 men, 225 women) who underwent PLIF were observed for >1 year. Factors investigated included the frequency of cage retropulsion and surgical revision. In addition, physical (age, sex, disease), surgical (fusion and PLIF levels, cage number, grade 2 osteotomy), and comorbid (DISH, existing vertebral fracture) factors were compared between patients with and without cage retropulsion. Factors related to surgical revision during the observation period were also considered. RESULTS: Cage retropulsion occurred in 15 patients and surgical revision was performed in 11. Revisions included the replacement of pedicle screws (PSs) with larger screws in all patients and supplementary implants in 10. Among the patients with cage retropulsion, the average PLIF level was 2.7, with DISH present in nine patients and existing vertebral fractures in six. Factors affecting cage retropulsion were diagnoses of osteoporotic vertebral fracture, multilevel fusion, single-cage insertion, grade 2 osteotomy, presence of DISH, and existing vertebral fracture. Multivariable analysis indicated that retropulsion of a fusion cage occurred significantly more frequently in patients with DISH and multilevel PLIF. CONCLUSIONS: DISH and multilevel PLIF were significant risk factors affecting cage retropulsion. Revision surgery for cage retropulsion revealed PS loosening, suggesting that implant replacement was necessary to prevent repeat cage retropulsion after revision.

Activities of Daily Living after Surgical Treatment for Osteoporotic Vertebral Fracture with or without Diffuse Idiopathic Skeletal Hyperostosis: A Retrospective Single-Institutional Study.

STUDY DESIGN: This investigation was a retrospective observational study. PURPOSE: The aim of this study was to evaluate whether having diffuse idiopathic skeletal hyperostosis (DISH) as a comorbidity affects the patient's ability to perform activities of daily living (ADL) after surgical treatment for osteoporotic vertebral fracture (OVF). OVERVIEW OF LITERATURE: A few studies have extensively evaluated elderly patients with comorbidities such as DISH and OVFinduced persistent back pain and their ability to perform ADL postoperatively. METHODS: In this study, 63 patients (21 men and 42 women) who underwent surgical treatment for OVF were enrolled. Of these patients, 26 had DISH (D+) and 37 did not have DISH (D-). Patient demographic characteristics and surgical, clinical, and radiological findings were compared between those with and without DISH. The change in their ability to perform ADL after surgery was also evaluated. RESULTS: Age, number of comorbidities, and 1-year mortality rate were significantly higher in the D+ group (p<0.05). Postoperative Visual Analog Scale (VAS) scores were significantly higher in patients with impaired (n=6, p=0.04) abilities to perform ADL, and improvements in VAS scores were significantly higher in patients with unchanged abilities to perform ADL (n=54, p=0.03) after surgery. The average postoperative VAS scores were 2.2 for the D+ group and 2.3 for the D- group, which were not significantly different. CONCLUSIONS: The frequency of OVF with DISH was higher in elderly men with multiple comorbidities and contributed to a higher 1-year mortality rate than those in patients without DISH. However, preoperative and postoperative VAS scores and improvements in VAS scores were similar between those with and without DISH. Postoperative impaired ability to perform ADL was associated with old age, high postoperative VAS scores, and little improvements in VAS scores, which were limitedly influenced by DISH. Surgical treatment of OVF combined with DISH is effective and appropriate for elderly patients.

Surgical Treatment of Osteoporotic Vertebral Fracture Associated with Diffuse Idiopathic Skeletal Hyperostosis along with Comparative Assessment of the Levels of Affected Vertebra or Anterior Column Reconstruction.

INTRODUCTION: Surgical treatment of osteoporotic vertebral fracture (OVF) often involves older patients with various comorbidities; thus, attending physicians must pay special attention to the invasiveness of surgical procedures and possible perioperative complications. In this retrospective observational study, we investigated the relationship between OVF and diffuse idiopathic skeletal hyperostosis (DISH) by examining the clinical characteristics and surgical outcomes. METHODS: Subjects comprised 26 patients (14 men, 12 women) who underwent surgical treatment for OVF complicated by DISH. Vertebral injuries affected the thoracolumbar transitional vertebrae in 18 patients and the middle and lower lumbar vertebrae in eight patients. The clinical characteristics, surgical results, radiological assessments, and outcomes were evaluated on the basis of the levels of affected vertebrae and whether anterior column reconstruction (ACR) was performed. RESULTS: Visual Analog Scale (VAS) measurements improved from an average of 69.7 mm before surgery to 21.3 mm after surgery. 14 patients had neurological deficits, who exhibited improvements by one or more steps on the Frankel scale after surgery. Activities of daily living (ADLs) were maintained during the six-month period following surgery in 23 patients. Comorbidity was observed in 22 patients. 14 patients had perioperative complications, and six required additional surgery. Both operating time and blood loss volume were significantly higher in patients in the middle and lower lumbar vertebrae and ACR groups. Postoperative correction loss was also significantly lower in the ACR group. CONCLUSIONS: Favorable degrees of improvement in neurological deficits and VAS were observed following surgery in patients with OVF complicated by DISH, and postoperative ADLs were maintained in 92% of the patients. Elderly men frequently presented with comorbidities, and the frequencies of patients with perioperative complications and those requiring additional surgery were high.